poly(2-(diethylamino)ethyl methacrylate)-based, ph-responsive, copolymeric mixed micelles for targeting anticancer drug control release

Quan Chen,1 Siheng Li,2 Zixiong Feng,1 Meng Wang,3 Chengzhi Cai,2 Jufang Wang,3 Lijuan Zhang1 1School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 2Department of Chemistry, University of Houston, Houston, TX, USA; 3School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: We have demonstrated a novel drug delivery system to improve the selectivity of the current chemotherapy by pH-responsive, polymeric micelle carriers. The micelle carriers were prepared by the self-assembly of copolymers containing the polybasic poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) block. The mixed copolymers exhibited a comparatively low critical micelle concentration (CMC; 1.95–5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug-loading content (24%) and entrapment efficiency (55%). Most importantly, the micelle carrier exhibited a pH-dependent conformational conversion and promoted the DOX release at the tumorous pH. Our in vitro studies demonstrated the comparable level of DOX-loaded mixed micelle delivery into tumor cells with the free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX-loaded mixed micelles were effective to inhibit the proliferation of tumor cells after prolonged incubation. Overall, the pH-responsive mixed micelle system provided desirable potential in the controlled release of anticancer therapeutics. Keywords: PDEAEMA, copolymers, pH-responsive, mixed micelle, DOX, targeting delivery